PROJECT SUMMARY/ABSTRACT This expansion of the Stress and Resilience in Dementia (STRIDE) study explores modifiable social-biological pathways associated with cognitive and brain-based Alzheimer?s disease and related dementia (ADRD) markers in a cohort of middle-aged and older members of a Midwestern tribal community. Incidence and prevalence of ADRD are rising across sociodemographic strata, but social disadvantage exacerbates risk and strong evidence suggests that African Americans and American Indian/Alaska Native (AI/AN) populations bear particularly high ADRD burden. Social and racial disparities in cognitive aging are clearly multifactorial but are currently underexplained. Intersecting disadvantage markers including race, geography, and socioeconomic status correlate with chronic exposure to stressors that can provoke neuroendocrine and vascular dysfunction and the premature onset of morbidity and age-related declines. However, AI/AN communities remain severely underrepresented in cognitive aging research, and ?weathering? processes that plausibly link socioenvironmental adversity to ADRD-associated brain and cognitive changes have not been explored. Social resources that promote resilience are also unknown. The long-term goal of this STRIDE project is to elucidate mechanisms by which social disadvantage contributes to ADRD risk in an underserved AI/AN community, and to pinpoint community-specific individual, social, and structural resources that mitigate that risk. The short-term objective of this pilot study is to identify social and biological factors associated with ADRD markers in a cohort of AI/AN community members, and establish preliminary methods and data that will facilitate future resilience-focused research. STRIDE builds on a partnership between the tribal Commission on Aging and the Wisconsin Alzheimer?s Disease Research Center (ADRC), and leverages rich existing cognitive and biomarker data available through the ADRC. The collection of multidimensional stress data including both self-reported burden and a validated index of physiological weathering allow for preliminarily modeling the influence of life-spanning stressors and resources on population-relevant ADRD markers. Aim 1: In a group of 80 AI/AN participants, examine relationships between social/physiological stress indices and markers of ADRD risk including (i) cognitive decline and (ii) in sub-set of AI/AN participants, key ADRD biomarkers such as ?-amyloid42. Aim 2 (Exploratory): Characterize self-reported social resources salient to AI/AN populations and examine (i) relationships with ADRD markers and (ii) modification of relationships in Aim 1 by relevant resources. Impact: Achieving STRIDE pilot aims will establish methods and early data on community-specific social determinants of cognitive health, and identify stress-linked biological mediators that can serve as proximal outcomes in future risk reduction studies. In so doing, STRIDE contributes to a growing body of research that seeks to recognize, understand, and reduce the growing ADRD crisis facing AI/AN communities.